Category Archives: Post Graduate

Recently, a new Cochrane Systematic Review on prophylactic vaccination against Human Papillomaviruses (HPV) to prevent cervical cancer and its precursors has been published. In view of the long post, I am not offering my own comments here.

Background Information:

Human papillomaviruses (HPV) are sexually transmitted and are common in young people. Usually they are cleared by the immune system. However, when high-risk (hr) types persist, they can cause the development of abnormal cervical cells, which are referred to as cervical precancer if at least two thirds of the surface layer of the cervix is affected.

Precancer can develop into cervical cancer after several years. Not everyone who has cervical precancer goes on to develop cervical cancer, but predicting who will is difficult.

There are a number of different hrHPV types which can cause cervical precancer and cancer. HPV16 and 18 are the most important high-risk types, since they cause about 70% of cervical cancers worldwide.

Preventive vaccination, by injection of HPV virus-like particles in the muscle, triggers the production of antibodies which protect against future HPV infections.

Key Messages:

Objectives:

The objectives of this review were:

To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women.

Methodology:

The investigators searched for Randomised Controlled Trials (RCTs) comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine).

They used Cochrane methodology and GRADE to rate the certainty of evidence for protection against

The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines

bivalent: RR 0.08 (0.03 to 0.23), high certainty;

quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty.

Data in older women were not available for this comparison

2. HPV16/18 negative

In those aged 15 to 26 years, HPV vaccines reduce

CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10).
*In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty).

In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.

B. Adverse effects

The risk of serious adverse events is similar between control and HPV vaccines in women of all ages.

Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty).

The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established.

C. Pregnancy outcomes

Among those who became pregnant during the studies, an increased risk of

The effects on congenital abnormalities and stillbirths are uncertain.

Cochrane Plain Language Summary

There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and women who are vaccinated between 15 and 26 years of age.

The protection is lower when a part of the population is already infected with HPV. Longer-term follow-up is needed to assess the impact on cervical cancer.

The vaccines do not increase the risk of serious adverse events, miscarriage or pregnancy termination. There are limited data from trials on the effect of vaccines on deaths, stillbirth and babies born with malformations.